Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In West Berlin in the autumn of 1975 through the following 5 months we observed 18 juvenile patients who had a toxic polyneuropathy and had sniffed a glue thinner. The neurological picture consisted of a symmetrical, progressive, ascending, mainly motor, polyneuropathy with pronounced muscle atrophy and characteristic vegetative alterations. The height of the disease was reached after 1 1/2-2 1/2 months and was characterized by tetraplegia in 7 patients. After 8 months all patients still had a motor deficit. Nerve biopsy showed paranodal axon swelling, dense masses of neurofilaments and secondary myelin retraction. The neurological and morphological data correspond to the "glue sniffer's neuropathy" and the n-hexane and MBK polyneuropathy after industrial exposure, as described in 10 cases to date. However, there was no MBK in the glue thinner. The polyneuropathies occurred in close time relation with the denaturation of the thinner with MEK (2-butanone). It is concluded from the data n-hexane and MBK have a common toxic mechanism with primary axonal changes and that there is an additional synergistic effect of MEK.
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PMID:Toxic polyneuropathies after sniffing a glue thinner. 6 97

MEK (2-butanone) when combined with MBK (2-hexanone) markedly enhanced MBK neurotoxicity. MBK in rat plasma after exposure to MBK/MEK increased with time. Metabolites of MBK identified in blood and urine of rats and guinea pigs were 2-hexanol and 2,5-hexanedione.
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PMID:Toxicity and metabolism of methyl n-butyl ketone. 17 51

The neurotoxicity of n-hexane is thought to be caused ultimately by 2,5-hexanedione (2,5-HD), one of the n-hexane metabolites. The potentiation of n-hexane neurotoxicity by co-exposure with MEK, therefore, is suspected to be related to kinetics of 2,5-HD in blood. To clarify the kinetics of n-hexane metabolites in the mixed exposure of n-hexane and MEK, rats were exposed to 2000 ppm n-hexane or a mixture of 2000 ppm n-hexane and 2000 ppm MEK, and the time courses of serum n-hexane metabolites were determined. 2,5-HD in serum increased until 2 h after the end of exposure, when serum 2,5-HD concentration reached a peak of 16.35 micrograms/ml in the n-hexane-alone group. In contrast, 2,5-HD in the mixed exposure group increased much more slowly during and after exposure than in the n-hexane-alone group. It reached a peak of 2.12 micrograms/ml at 8 h after the end of exposure. Serum MBK, a precursor of 2,5-HD in the co-exposure group, was about half in the n-hexane-alone group during exposure. However, MBK decreased more slowly in the co-exposure group than in the n-hexane-alone group after the end of the exposure. The results suggest that co-exposed MEK might inhibit oxidation of n-hexane and decrease clearance of n-hexane metabolites. Co-exposed MEK did not increase serum 2,5-HD, which was considered a main neurotoxic metabolite. Therefore the enhancement of neurotoxicity could not be attributed to increased serum 2,5-HD in the co-exposed group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of MEK on kinetics of n-hexane metabolites in serum. 237 36

Potentiation of haloalkane hepatonecrosis by various ketones is a well-documented observation. The present study investigates the hepatobiliary effects of such treatments. Male Sprague-Dawley rats were pretreated with acetone (A), 2-butanone (MEK), 2-hexanone (MBK), 15 mmol/kg (po), or chlordecone (CD) and its nonketonic analog, mirex (M), 50 mg/kg (po). Following the pretreatment at various time intervals ranging from 10 to 96 hr, groups of animals received a challenging dosage of CHCl3 (0.5 ml/kg, po). In a collateral experiment, groups of animals were pretreated with vehicle and 18 hr later received either 0.50, 0.75, or 1.00 ml/kg CHCl3 (po). In each case hepatobiliary function was evaluated 24 hr later using bile flow rate and plasma bilirubin concentration. The results showed (1) that the ketones alone had no effect; mirex alone increased bile flow; (2) CHCl3 alone had no effect on bile flow but slightly increased plasma bilirubin; (3) all pretreatments potentiated the effect of CHCl3 on plasma bilirubin; (4) combinations of A, MBK, or CD plus CHCl3 were cholestatic within a restricted time frame. A study of biliary tree permeability by the segmented retrograde intrabiliary injection technique, using mannitol and inulin as marker compounds, suggested that cholestasis may result from potentiation of CHCl3-induced alterations in canalicular membrane permeability.
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PMID:Modifications in rat hepatobiliary function following treatment with acetone, 2-butanone, 2-hexanone, mirex, or chlordecone and subsequently exposed to chloroform. 242 88

It is well known that n-hexane produces peripheral neuropathy, and 2,5-hexanedione, one of the metabolites of n-hexane, is thought to be the main causative agent. Recently, the metabolites of n-hexane in urine have been measured by gas chromatography, and 2,5-hexanedione was proved to be useful for the biological monitoring of n-hexane exposure. In the present experiment, we intended to clarify the change of n-hexane metabolites in the urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene of MEK. In the first experiment, five separate groups of five rats each were exposed to 100, 500, 1000, or 3000 ppm of n-hexane, or fresh air respectively in an exposure chamber for 8 h a day. Urinary samples were gathered during exposure, 16, 24, and 40 h after exposure. Half of each sample was analyzed by gas chromatography after hydrolysis with acid and enzymes, and the other half was analyzed without hydrolysis. 2,5-Dimethylfuran, MBK, 2-hexanol, 2,5-hexanedione, and gamma-valerolactone could be identified as n-hexane metabolites in the urine. The main metabolites were 2-hexanol and 2,5-hexanedione. 2-Hexanol was mostly excreted during exposure, while most of the 2,5-hexanedione was excreted after the end of exposure. The amount of metabolites in the urine correlatively increased with the concentration of n-hexane from 100 to 1000 ppm, but the amount of metabolites scarcely increased when the concentration of n-hexane increased from 1000 to 3000 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes of n-hexane metabolites in urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene or MEK. 665 98